A Phase I Study of the Hsp90 Inhibitor AUY922 plus Capecitabine for the Treatment of Patients with Advanced Solid Tumors

Background: This phase I study determined the maximum tolerated dose (MTD) of AUY922 with capecitabine in advanced solid tumors. Methods: Capecitabine 1000mg/m(2) PO BID was administered with escalating doses of AUY922 IV; the MTD of AUY922 was combined with capecitabine 1250mg/m(2) (DL6). Results: 23 patients were treated at 5 dose levels (22mg/m(2)-70mg/m(2)). No DLTs were observed until DL6 (grade 3 diarrhea). Reversible vision darkening was seen in 26%. Four patients had partial response; 2 previously progressed on fluorouracil. Eight patients had stable disease (median 25.5 weeks). Conclusion: AUY922 plus capecitabine was well-tolerated up to 70mg/m(2) with encouraging preliminary efficacy.